scholarly journals Circular RNA circ_0032462 Enhances Osteosarcoma Cell Progression by Promoting KIF3B Expression

2020 ◽  
Vol 19 ◽  
pp. 153303382094321
Author(s):  
Rui Gu ◽  
Xiaodong Li ◽  
Xiaowei Yan ◽  
Zhen Feng ◽  
Aixin Hu
Keyword(s):  
Family Member ◽  
Messenger Rna ◽  
Circular Rna ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Cell Progression ◽  
Kinesin Family

Circular RNAs are a recently discovered subclass of endogenous noncoding RNAs that have been confirmed to play an important role in various pathophysiological processes. However, the underlying function of circular RNAs in osteosarcoma still remains unclear. We aimed to comprehend the function of circ_0032462 in osteosarcoma, as it has been predicted to be highly expressed in osteosarcoma cells. Using real-time polymerase chain reaction, we verified the elevated expression of circ_0032462 in osteosarcoma cells than normal cells. Functional validation experiments revealed that circ_0032462 overexpression promoted proliferation, migration, and invasion in osteosarcoma cells, whereas circ_0032462 silencing was observed to inhibit cancer cell progression (proliferation, migration, and invasion). Furthermore, we found that circ_0032462 upregulated the messenger RNA and protein expression level of kinesin family member 3B. In addition, kinesin family member 3B inhibition was found to inhibit circ_0032462-induced enhanced osteosarcoma cell progression. circ_0032462 overexpression was observed to reverse circ_0032462 silencing-induced inhibitory effect on osteosarcoma cell progression. Overall, our research revealed the function of circ_0032462 in osteosarcoma progression, which might serve as a novel chemotherapeutic target for osteosarcoma.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lanlan Xi ◽  
Quanlin Liu ◽  
Wei Zhang ◽  
Linshan Luo ◽  
Jingfeng Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Protein Levels ◽  
Cell Progression ◽  
Rna Immunoprecipitation ◽  
Induced Apoptosis

Abstract Background Circular RNAs (circRNAs) have been reported to play vital roles in colorectal cancer (CRC). However, only a few circRNAs have been experimentally validated and functionally described. In this research, we aimed to reveal the functional mechanism of circCSPP1 in CRC. Methods 36 DOX sensitive and 36 resistant CRC cases participated in this study. The expression of circCSPP1, miR-944 and FZD7 were detected by quantitative real time polymerase chain reaction (qRT-PCR) and the protein levels of FZD7, MRP1, P-gp and LRP were detected by western blot. Cell proliferation, migration, invasion, and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, or flow cytometry analysis, respectively. The interaction between miR-944 and circCSPP1 or frizzled-7 (FZD7) was predicted by Starbase 3.0 and verified by the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Xenograft tumor assay was performed to examine the effect of circCSPP1 on tumor growth in vivo. Results The expression of circCSPP1 and FZD7 was upregulated while miR-944 expression was downregulated in doxorubicin (DOX)-resistant CRC tissues and cells. CircCSPP1 knockdown significantly downregulated enhanced doxorubicin sensitivity, suppressed proliferation, migration, invasion, and induced apoptosis in DOX-resistant CRC cells. Interestingly, we found that circCSPP1 directly downregulated miR-944 expression and miR-944 decreased FZD7 level through targeting to 3′ untranslated region (UTR) of FZD7. Furthermore, circCSPP1 mediated DOX-resistant CRC cell progression and doxorubicin sensitivity by regulating miR-944/FZD7 axis. Besides, circCSPP1 downregulation dramatically repressed CRC tumor growth in vivo. Conclusion Our data indicated that circCSPP1 knockdown inhibited DOX-resistant CRC cell growth and enhanced doxorubicin sensitivity by miR-944/FZD7 axis, providing a potential target for CRC therapy.

scholarly journals Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fei Pan ◽  
Dongqing Zhang ◽  
Na Li ◽  
Mei Liu
Keyword(s):  
Colorectal Cancer ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Small Interfering Rnas ◽  
Regulatory Relationship ◽  
Downstream Target ◽  
Normal Tissues

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

scholarly journals EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Renjie Wang ◽  
Sai Zhang ◽  
Xuyi Chen ◽  
Nan Li ◽  
Jianwei Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioblastoma Multiforme ◽  
Aurora Kinase ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Reporter Assays

Abstract Background Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). Methods A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. Results In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. Conclusions Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM. Graphical abstract

scholarly journals MiR-92a modulates proliferation, apoptosis, migration, and invasion of osteosarcoma cell lines by targeting Dickkopf-related protein 3

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Haiyang Yu ◽  
Hang Song ◽  
Li Liu ◽  
Shuo Hu ◽  
Yuxin Liao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Related Protein ◽  
Flow Cytometric ◽  
Regulatory Impact ◽  
Direct Binding ◽  
And Diffusion

Abstract Osteosarcoma (OS) is recognized as a common malignant tumor with a high trend of metastasis and diffusion. Despite the progresses that have been made in surgery, chemotherapy, and radiotherapy in the recent decades, the prognosis of patients with OS still remains poor. MiRNAs are being increasingly considered as new therapeutic targets for OS treatment. Our research aims to investigate the regulatory impact of miR-92a in the development of OS. Quantitative real-time PCR (qRT-PCR) results revealed that the expression of miR-92a was aberrantly overexpressed in human OS cell lines. By using cell counting kit-8 (CCK-8) assays, colony formation assays, flow cytometric analyses and Transwell assays, our data suggested that up-regulation of miR-92a promoted the proliferation, migration, and invasion of MNNG and U2OS cells, while inhibiting their apoptosis. In contrast, the knockdown of miR-92a effectively reversed these cellular biological behaviors. Furthermore, bioinformatics analysis indicated that Dickkopf-related protein 3 (DKK3) was a possible target of miR-92a. Subsequently, negative regulation of miR-92a on DKK3 was observed, which further supported the direct binding between them. In addition, silencing DKK3 rescued the inhibitory effect of miR-92a inhibitor on the development of OS. To sum up, our study revealed that miR-92a played a carcinogenic role in the growth of OS by promoting the tumorigenesis of OS cells via targeting of DKK3, thus revealing a new therapeutic target for OS.

scholarly journals Circular RNA hsa_circ_0007142 Is Upregulated and Targets miR-103a-2-5p in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chang-li Zhu ◽  
Xiaofeng Sha ◽  
Yuan Wang ◽  
Jin Li ◽  
Men-yan Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bioinformatic Analysis ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Poor Differentiation ◽  
Hct 116 Cells

Circular RNAs (circRNAs) are a large class of endogenous noncoding RNAs that regulate gene expression and mainly function as microRNA sponges. This study aimed to explore the aberrant expression of circRNAs in colorectal cancer (CRC). Using a circRNA microarray, we identified 892 differentially expressed circRNAs between six pairs of CRC and adjacent paracancerous tissues. Among them, hsa_circ_0007142 was significantly upregulated. Further analysis in 50 CRC clinical samples revealed that hsa_circ_0007142 upregulation was associated with poor differentiation and lymphatic metastasis of CRC. Bioinformatic analysis and luciferase reporter assay showed that hsa_circ_0007142 targeted miR-103a-2-5p in CRC cells. Moreover, the silencing of hsa_circ_0007142 by siRNAs decreased the proliferation, migration, and invasion of HT-29 and HCT-116 cells. Taken together, these findings suggest that hsa_circ_0007142 is upregulated in CRC and targets miR-103a-2-5p to promote CRC.

Circ_0007031 enhances tumor progression and promotes 5-fluorouracil resistance in colorectal cancer through regulating miR-133b/ABCC5 axis

2020 ◽  
Vol 29 (4) ◽  
pp. 531-542
Author(s):  
Xiaowen He ◽  
Jun Ma ◽  
Mingming Zhang ◽  
Jianhua Cui ◽  
Hao Yang
Keyword(s):  
Colorectal Cancer ◽  
Colony Formation ◽  
Human Cancer ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression ◽  
Rna Immunoprecipitation

Colorectal cancer (CRC) remains one of the most commonly diagnosed malignancies worldwide. Circular RNAs (circRNAs) are being found to play crucial roles in human cancer, including CRC. The purpose of this study was to explore the function and mechanism of circ_0007031 on CRC progression and 5-fluorouracil (5-FU) resistance. The levels of circ_0007031, ATP-binding cassette subfamily C member 5 (ABCC5) and miR-133b were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell survival and proliferation were detected by the 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell colony formation was evaluated using a standard colony formation assay. Transwell assays were performed to determine cell migration and invasion. Targeted correlations among circ_0007031, miR-133b and ABCC5 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Animal experiments were performed to observe the role of circ_0007031 in vivo. Our data indicated that circ_0007031 up-regulation was associated with CRC resistance to 5-FU. Circ_0007031 knockdown repressed CRC cell proliferation, migration and invasion and enhanced 5-FU sensitivity. Circ_0007031 directly interacted with miR-133b. Moreover, circ_0007031 knockdown regulated CRC cell progression and 5-FU sensitivity by miR-133b. ABCC5 was a direct target of miR-133b, and circ_0007031 mediated ABCC5 expression via acting as a miR-133b sponge. Furthermore, miR-133b overexpression regulated CRC cell progression and sensitivity to 5-FU by down-regulating ABCC5. Additionally, circ_0007031 knockdown suppressed tumor growth in vivo. Our current work had led to the identification of circ_0007031 knockdown that repressed CRC cell malignant progression and enhanced 5-FU sensitivity via regulating ABCC5 expression by sponging miR-133b.

scholarly journals Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells

2016 ◽  
Vol 24 (5) ◽  
pp. 381-389 ◽  
Author(s):  
Feng Jiang ◽  
Yan Shi ◽  
Hong Lu ◽  
Guojun Li
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Mesenchymal Transition ◽  
Armadillo Repeat ◽  
Proliferation And Invasion

Armadillo repeat-containing protein 8 (ARMC8) plays an important role in regulating cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. However, the expression pattern and role of ARMC8 in osteosarcoma are still unclear. In this study, our aims were to examine the effects of ARMC8 on osteosarcoma and to explore its underlying mechanism. Our results demonstrated that ARMC8 was overexpressed in osteosarcoma cell lines. Knockdown of ARMC8 significantly inhibited osteosarcoma cell proliferation in vitro and markedly inhibited xenograft tumor growth in vivo. ARMC8 silencing also suppressed the epithelial‐mesenchymal transition (EMT) phenotype, as well as inhibited the migration and invasion of osteosarcoma cells. Furthermore, knockdown of ARMC8 obviously inhibited the expression of β-catenin, c-Myc, and cyclin D1 in MG-63 cells. In conclusion, this report demonstrates that ARMC8 silencing inhibits proliferation and invasion of osteosarcoma cells. Therefore, ARMC8 may play an important role in the development and progression of human osteosarcoma and may represent a novel therapeutic target in the treatment of osteosarcoma.

scholarly journals CircSEC24A promotes colorectal cancer progression by regulating miR-488-3p/TMEM106B axis

2020 ◽  
Author(s):  
Gaowu Hu ◽  
Wei Peng ◽  
Yongqing Cao
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transmembrane Protein ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression

Abstract Background: Currently, more and more circular RNAs (circRNAs) have been identified to exert their functions in tumor progression, including colorectal cancer (CRC). However, the role of circSEC24A (circ_0003528) in CRC remains unknown.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circSEC24A, SEC24A and microRNA-488-3p (miR-488-3p). The characterization of circSEC24A was investigated by Actinomycin D and RNase R digestion assays. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to assess cell proliferation. Flow cytometry analysis was adopted for cell apoptosis and cell cycle process. Transwell assay was employed to evaluate cell migration and invasion. Western blot assay was performed to determine protein levels. Dual-luciferase reporter assay was utilized to explore the relationship between miR-488-3p and circSEC24A or transmembrane protein 106B (TMEM106B). Murine xenograft model was constructed to explore the effect of circSEC24A in vivo .Results: CircSEC24A level was increased in CRC tissues and cells. CircSEC24A deficiency impeded cell proliferation, cell cycle process, migration and invasion and induced apoptosis in CRC cells in vitro and blocked tumorigenesis in vivo . MiR-488-3p was a target of circSEC24A and miR-488-3p was downregulated in CRC tissues and cells. The inhibitory effect of circSEC24A silencing on CRC cell progression was restored by miR-488-3p inhibition. Moreover, TMEM106B could be negatively regulated by miR-488-3p via acting as a downstream gene of miR-488-3p. MiR-488-3p overexpression decelerated CRC cell progression by targeting TMEM106B.Conclusion: CircSEC24A facilitated CRC progression by regulating miR-488-3p/TMEM106B axis, which might provide a promising treatment approach for CRC.

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